N-Acetylcysteine in Critically Ill Patients Undergoing Contrast Enhanced Computed Tomography

NCT ID: NCT00830193

Last Updated: 2009-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31
• Study Completion Date: 2005-05-31

Brief Summary

Critically ill patients frequently undergo contrast enhanced computed tomography (CT) to establish diagnoses and direct management. Contrast agents can disturb kidney function and result in kidney dysfunction. The investigators investigated the effects of high dose N-acetylcysteine (NAC) or placebo, in addition to hydration, in preventing kidney dysfunction following contrast enhanced CT) in critically ill adults in the intensive care units of two teaching hospitals.

Detailed Description

Potential participants were identified by staff intensivists or resident physicians following admission to participating ICUs. We included critically ill adult patients at least 18 years of age who consented to participate in the trial, had central venous access and a foley catheter, required a contrast-enhanced CT of any organ system(s), and were considered 'at risk' for the development of CIN. We defined 'at risk' to include patients with at least one of the following at the time of randomization (i) a serum creatinine of > 106 µmol/L and or urea > 6 mmol/L, (ii) urine output of < 0.5 cc/kg over > 4 hrs or (iii) an increase in serum creatinine of > 50 µmol/L in < 24 hours. We stratified based on the presence or absence of diabetes defined as a history of treatment with oral hypoglycemics or insulin.

We excluded patients with a (i) CK > 5,000 or the presence of myoglobinuria, (ii) a known allergy or hypersensitivity reaction to radiographic contrast dye or NAC, (iii) serious illness with imminent threat of dying (low likelihood of survival within 48-hours) or poor prognosis, (iv) pregnancy, (v) patients with cardiogenic shock (NYHA class 3 or 4 symptoms), (vi) known or suspected nephritic, nephrotic or pulmonary-renal syndromes, (vii) a post renal etiology of renal impairment, (viii) previous renal transplant, (ix) known solitary kidney, (x) serum creatinine > 200 µmol/L or (xi) recent exposure to radiographic contrast within 14 days of randomization.

The primary outcome for the study was the development of CIN defined as a rise in serum creatinine of > 50 µmol/L from the time of randomization up to day 5 following contrast exposure.

Secondary outcomes included ICU and hospital length of stay, ICU and hospital mortality and the requirement for renal replacement therapy. We recorded compliance with assigned treatment and assessed for development of severe unexpected adverse events defined as hypotension, bronchospasm and anaphylactic reactions.

Conditions

Contrast Induced Nephropathy; Critically Ill

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

N-acetylcysteine

Intravenous fluid administration was administered as soon as possible following randomization (not to exceed 12 hours prior to anticipated contrast exposure) and continued for 12 hours post CT. Patients randomized to the experimental arm received intravenous normal saline plus NAC 10 grams IV (5 g pre and 2.5 g at 6 and 12 hours post-exposure) for a total of 3 doses.

Group Type: ACTIVE_COMPARATOR

N-acetylcysteine

Intervention Type: DRUG

Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g of NAC or placebo in 100 cc D5W (pre-CT dose) or 2.5 g of NAC or placebo in 50 cc D5W (post-CT doses).

Placebo

Intravenous fluid administration was administered as soon as possible following randomization (not to exceed 12 hours prior to anticipated contrast exposure) and continued for 12 hours post CT. Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g in 100 cc D5W (pre-CT dose) or 2.5 g in 50 cc D5W (post-CT doses). The placebo was D5W and was colour and consistency matched by pharmacy. Patients randomized to placebo received intravenous normal saline plus 3 doses of placebo.

Group Type: PLACEBO_COMPARATOR

D5W Placebo

Intervention Type: DRUG

Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g of NAC or placebo (D5W) in 100 cc D5W (pre-CT dose) or 2.5 g NAC or placebo in 50 cc D5W (post-CT doses).

Interventions

N-acetylcysteine

Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g of NAC or placebo in 100 cc D5W (pre-CT dose) or 2.5 g of NAC or placebo in 50 cc D5W (post-CT doses).

Intervention Type: DRUG

D5W Placebo

Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g of NAC or placebo (D5W) in 100 cc D5W (pre-CT dose) or 2.5 g NAC or placebo in 50 cc D5W (post-CT doses).

Intervention Type: DRUG

Other Intervention Names

Mucomyst; D5W

Eligibility Criteria

Inclusion Criteria

• The investigators included critically ill adult patients at least 18 years of age who consented to participate in the trial, had central venous access and a foley catheter, required a contrast-enhanced CT of any organ system(s), and were considered 'at risk' for the development of CIN.
• The investigators defined 'at risk' to include patients with at least one of the following at the time of randomization (i) a serum creatinine of > 106 µmol/L and or urea > 6 mmol/L, (ii) urine output of < 0.5 cc/kg over > 4 hrs or (iii) an increase in serum creatinine of > 50 µmol/L in < 24 hours.

Exclusion Criteria

• The investigators excluded patients with a

• CK > 5,000 or the presence of myoglobinuria
• a known allergy or hypersensitivity reaction to radiographic contrast dye or NAC
• serious illness with imminent threat of dying (low likelihood of survival within 48-hours) or poor prognosis
• pregnancy
• patients with cardiogenic shock (NYHA class 3 or 4 symptoms)
• known or suspected nephritic, nephrotic or pulmonary-renal syndromes
• a post renal etiology of renal impairment
• previous renal transplant
• known solitary kidney
• serum creatinine > 200 µmol/L or (xi) recent exposure to radiographic contrast within 14 days of randomization.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Martin, Claudio M., M.D.

INDIV

Sponsor Role: collaborator

Fran Priestap

UNKNOWN

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

London Health Sciences Centre - Victoria Hospital

Principal Investigators

Claudio M Martin, MD, FRCPC, MSc

Role: STUDY_DIRECTOR

London Health Sciences Centre - Victoria Hospital

Locations

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

London Health Sciences Centre - University Hospital Campus

London, Ontario, Canada

Countries

Canada

Other Identifiers

LHRI-000001

Identifier Type: -

Identifier Source: org_study_id